The present invention relates to benzamide derivatives which are useful as antiemetic and/or antipsychotic agents. In the preferred embodiments of the invention, administration of the agents is not accompanied by mammary hypertrophy.
U.S. Pat. No. 3,342,826 discloses numerous benzamide derivatives which are useful as antipsychotic and antiemetic agents. Among the compounds disclosed in the patent are 2-methoxy-N-(1-ethyl-2-pyrrolidinylmethyl)-5-sulfamoyl benzamide (so-called Sulpiride), 3,5 dichloro-N-(1-ethyl-2-pyrrolidinylmethyl)-2-methoxybenzamide, and 5-bromo-N-(1-ethyl-2-pyrrolidinylmethyl)-2-methoxy benzamide.
Benzamide derivatives function by blocking dopamine receptors. An undesirable side effect which accompanies the administration of prior derivatives like Sulpiride is mammary hypertrophy which is caused by an increase in the release of prolactin. Prolactin is formed and secreted by the pituitary gland and its release is regulated by prolactin inhibiting factor or PIF. PIF is found in the hypothalmus and there are indications that PIF is under dopaminergic control. Thus, it is believed that when the dopamine receptors are blocked by benzamide derivatives, PIF is not secreted and there is an elevation in prolactin levels which results in mammary hypertrophy.
The hormonal imbalance observed with sulpiride and its analogues raises questions as to the safety of the compounds. Many tumors and cancers are hormonally activated. Thus, it is possible that the administration of Sulpiride may trigger a neoplasm or worsen a pre-existing tumor. Moreover, breast engorgement, galactorrhea, and amenorrhea, which are caused by prolactin, are particularly troublesome side effects in female patients. Thus, there is a need for antiemetic and antipsychotic agents which do not cause mammary hypertrophy.